双硫仑对肿瘤相关巨噬细胞分泌细胞因子基因表达的影响

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摘要目的研究双硫仑（DSF）对口腔鳞状细胞癌（OSCC）肿瘤细胞上清液诱导肿瘤相关巨噬细胞（TAMs）分泌的细胞因子基因表达的影响。方法将RAW264.7细胞随机分为对照组和研究组，研究使用两种诱导方法，第一种诱导方式为对照组用CAL27肿瘤细胞上清诱导RAW264.7细胞48 h，研究组在CAL27肿瘤细胞上清液诱导RAW264.7细胞的同时加入DSF/葡萄糖酸铜（DSF/Cu）2 μmol/L干预48 h；第二种诱导方式为对照组用CAL27肿瘤细胞上清诱导RAW264.7细胞48 h后，继续诱导48 h，研究组CAL27肿瘤细胞上清诱导RAW264.7细胞48 h后，用DSF/Cu 2 μmol/L干预48 h。检测两种诱导方式下，一氧化氮合酶（iNOS）、白细胞介素12（IL-12）、肿瘤坏死因子-α（TNF-α）、精氨酸酶1（Arg-1）、IL-10的基因表达情况。结果诱导过程中加入DSF/Cu，研究组iNOS mRNA水平高于对照组，Arg-1 mRNA水平低于对照组，差异均有高度统计学意义（均P ＜ 0.01）。两组IL-12、TNF-α、IL-10 mRNA水平，差异无统计学意义（P ＞ 0.05）。诱导48 h后加入DSF/Cu，研究组iNOS mRNA、IL-12 mRNA、TNF-α mRNA、IL-10 mRNA水平高于对照组，Arg-1 mRNA水平低于对照组，差异有统计学意义（P ＜ 0.05或P ＜ 0.01）。结论 DSF可调节TAMs分泌细胞因子的基因表达，有助于进一步阐明DSF抗OSCC的作用机制，可能为将来口腔肿瘤的诊治提供实验依据和治疗策略。

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	张雯雯1 刘璐瑶1 曹娟1 李玮柏1 董春玲2 李波1

关键词 ：双硫仑, 葡萄糖酸铜, 肿瘤相关巨噬细胞, 口腔鳞状细胞癌

Abstract：Objective To study the effect of Disulfiram (DSF) on the genes expression of cytokine secreted by tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) tumor cell supernatant. Methods RAW264.7 cells were randomly divided into control group and research group. Two induction methods were used, the first inducement was that CAL27 tumor cell supernatant was used to induce RAW264.7 cells for 48 h in control group; and DSF and copper gluconate (DSF/Cu) 2 μmol/L were added to the CAL27 tumor cell supernatant to induce RAW264.7 cells for 48 h in research group. The second inducement was that RAW264.7 cells were induced with CAL27 tumor cell supernatant for 48 h, and then continued to be induced for 48 h in control group; in research group, after CAL27 tumor cell supernatant induced RAW264.7 cells for 48 h, DSF/Cu 2 μmol/L was used to intervene for 48 h. The gene expression levels of nitric oxide synthase (iNOS), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), argininase 1 (Arg-1) and IL-10 were measured. Results DSF/Cu was added in the induction process, iNOS mRNA level of research group was higher than that of control group, Arg-1 mRNA level was lower than that of control group, and the differences were highly statistically significant (all P < 0.01). There were no significant differences in IL-12, TNF-α and IL-10 mRNA levels between two groups (P > 0.05). DSF/Cu was added 48 h after induction, iNOS mRNA, IL-12 mRNA, TNF-α mRNA, IL-10 mRNA levels in research group were higher than those in control group, and Arg-1 mRNA level was lower than that in control group, with statistically significant differences (P < 0.05 or P < 0.01). Conclusion DSF can regulate the gene expression of cytokines secreted by TAMs, which helps to further clarify the mechanism of disulfiram against OSCC. It may provide experimental basis and treatment strategies for the diagnosis and treatment of oral tumors in the future.

Key words： Disulfiram Copper gluconate Tumor-associated macrophages Oral squamous cell carcinoma

基金资助:吉林省教育厅“十三五”科学技术项目（JJKH201 70839KJ）；
吉林省财政厅优秀中青年骨干人才项目（JCSZ20 19378-14）；
吉林省科技发展计划国际科技合作项目（2017 0414053GH）；
吉林省卫生计生青年科技骨干培养计划项目（2016Q020）；
吉林省卫生计生科研计划项目（2015Z007）；
吉林大学白求恩计划科研项目（2018B27）。

通讯作者: 李波（1977.11-），男，博士，副教授，硕士生导师；研究方向：口腔肿瘤的发病机制及干预。董春玲（1976.4-），女，博士，主任医师，硕士生导师；研究方向：炎症与肿瘤的发病机制及干预。

作者简介: 张雯雯（1993.9-），女，吉林大学口腔医学院2017级口腔医学专业在读硕士研究生；研究方向：口腔肿瘤的发病机制及干预。

引用本文:

张雯雯1 刘璐瑶1 曹娟1 李玮柏1 董春玲2 李波1. 双硫仑对肿瘤相关巨噬细胞分泌细胞因子基因表达的影响[J]. 中国医药导报, 2020, 17(23): 12-15.
ZHANG Wenwen1 LIU Luyao1 CAO Juan1 LI Weibo1 DONG Chunling2 LI Bo1. Effect of Disulfiram on gene expression of cytokines secreted by tumor-associated macrophages. 中国医药导报, 2020, 17(23): 12-15.

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